Methods for the formation of aryl-sulfur bonds are indispensable tools in synthetic chemistry. Their importance stems from the prevalence of aryl-sulfur bonds in many molecules that are of biological, pharmaceutical and materials interest. Similarly, diaryl selenides have attracted considerable interest because of their potential as anticancer and antioxidant agents. They are also key intermediates in the synthesis of a plethora of biologically and pharmaceutically important selenium compounds such as selenonium salts, selenoxides, selenimines, and selenide dihalides. In recognition of their importance, various synthetic methods for the formation of diaryl selenides have been reported in the literature.
Traditional methods for the synthesis of aryl-sulfur bonds often require harsh reaction conditions. For example, coupling of copper thiolates with aryl halides requires polar solvents such as HMPA and temperatures around 200° C. Reduction of aryl sulfones or aryl sulfoxides requires strong reducing agents such as DIBAL-H or LiAlH4. Likewise, earlier selenide preparatory methods often required photochemical or harsh reaction conditions such as the use of polar, toxic solvents such as HMPA and high reaction temperatures. Other reported protocols include the reaction of aryl halide and benzeneselenate anion in liquid ammonia under UV light and the reaction of sodium selenide with arenediazonium salts.
In 1980, Migita and co-workers first reported the cross-coupling reaction of aryl halides and thiols with Pd(PPh3)4 as the catalyst and NaOt-Bu as the base in polar solvents such as refluxing ethanol or DMSO at 90° C. Thereafter, however, few reports have appeared in the literature for the formation of aryl-sulfur bonds using transition metal catalysts, and then only for Pd(0) or Ni(0)—in sharp contrast to the volume of literature that exists for the formation of aryl-nitrogen and aryl-oxygen bonds. In 1996, following Hartwig's mechanistic studies on the reductive elimination of palladium(II) arylthiolate complexes with chelating phosphines, Zheng and co-workers reported the first general palladium-based protocol for the synthesis of aryl sulfides from aryl triflates. More recently, in 2001, Schopfer and Schlapbach reported a general palladium-catalyzed method for the synthesis of aryl sulfides from aryl iodides, in toluene, using DPEPhos as the ligand.
The current state of aryl-selenium chemistry can be viewed from an analogous historical perspective. In recent years, only a handful of reports have appeared in the literature with synthetic protocols for the formation of aryl-selenium bonds that are general, mild and tolerant. In 1985, Cristau and co-workers first showed that aryl selenides can be obtained by a cross-coupling reaction of aryl halides and sodium benzeneselenolate using Ni(II)-based catalysts. In 2000, Millois and Diaz modified and extended Cristau's method to accommodate diaryl diselenide as a starting material instead of sodium benzeneselenolate. Very recently, the groups of Nishiyama and Beletskaya have independently reported protocols for the cross coupling reaction of aryl iodides and PhSeSnBu3 using palladium-based catalysts.
Various concerns in the art, however, continue to prompt development of new catalytic systems. In particular, the price of palladium is prohibitive, having risen by about 900% in recent years. Further, expensive ligands are required for employment of palladium in reactions of interest. As a result, alternate metals and ligand systems have been the subject of increased study. One such approach involves copper-based systems. Traditional copper-mediated reactions suffer from drawbacks such as high reaction temperatures, the use of copper salts in greater than stoichiometric amounts, sensitivity to functional groups on the aryl halide and irreproducibility. Yet, they remain as the reactions of choice in large- and industrial-scale syntheses. As such, in the past five years, there has been a resurgence in interest in developing mild synthetic methods based on copper-based catalysts as an alternative to palladium(0) catalysts for the formation of aryl-carbon and aryl-heteroatom bonds. In this regard, several research groups have reported copper-based methods for the formation of aryl-carbon, aryl-nitrogen and aryl-oxygen bonds. In addition to being simple and mild, these protocols also accommodate substrates that do not otherwise undergo coupling by palladium catalysis. Moreover, from an economic standpoint and in comparison to palladium, copper-based catalysts are quite attractive. However, several concerns remain, as such catalytic systems have shown limited utility—in particular, with respect to the formation of aryl-sulfur and/or aryl-selenium bonds.